In vivo imaging of glycol chitosan-based nanogel biodistribution

The preclinical development of nanomedicines raises several challenges and requires a comprehensive characterization. Among them is the evaluation of the biodistribution following systemic administration. In previous work, the biocompatibility and in vitro targeting ability of a glycol chitosan (GC) based nanogel have been validated. In the present study, its biodistribution in the mice is assessed, using near-infrared (NIR) fluorescence imaging as a tool to track the nanogel over time, after intravenous administration. Rapid whole body biodistribution of both Cy5.5 labeled GC nanogel and free polymer is found at early times. It remains widespreadly distributed in the body at least up to 6 h postinjection and its concentration then decreases drastically after 24 h. Nanogel blood circulation half-life lies around 2 h with the free linear GC polymer presenting lower blood clearance rate. After 24 h, the blood NIR fluorescence intensity associated with both samples decreases to insignificant values. NIR imaging of the organs shows that the nanogel had a body clearance time of 48 h, because at this time point a weak signal of NIR fluorescence is observed only in the kidneys. Hereupon it can be concluded that the engineered GC nanogel has a fairly long blood circulation time, suitable for biomedical applications, namely, drug delivery, simultaneously allowing efficient and quick body clearance.

Acellular Gellan-gum based bilayered structures for the regeneration of osteochondral defects: a preclinical study

 In orthopaedics, the management and treatment of osteochondral (OC) defects remains an ongoing clinical challenge. Autologous osteochondral mosaicplasty has been used as a valid option for OC treatments although donor site morbidity remains a source of concern [1]. Engineering a whole structure capable of mimicking different tissues (cartilage and subchondral bone) in an integrated manner could be a possible approach to regenerate OC defects. In our group we have been proposing the use of bilayered structures to regenerate osteochondral defects [2,3]. The present study aims to investigate the pre-clinical performance of bilayered hydrogels and spongy-like hydrogels in in vivo  models (mice and rabbit, respectively), in both subcutaneous and orthotopic models. The bilayered structures were produced from Low Acyl Gellan Gum (LAGG) from Sigma-Aldrich, USA. Cartilage-like layers were obtained from a 2wt% LAGG solution. The bone-like layers were made of 2wt% LAGG with incorporation of hydroxyapatite at 20% and 30% (w/v). Hydrogels and spongy-like were subcutaneouly implanted in mice to evaluate the inflammatory response. Then, OC defects were induced in rabbit knee to create a critical size defect (4 mm diameter and 5 mm depth), and then hydrogels and sponges implanted. Both structures followed different processing methods. The hydrogels were injected allowing in situ  crosslinking. Unlike, the spongy-like were pre-formed by freeze-drying. The studies concerning subcutaneous implantation and critical size OC defect were performed for 2 and 4 weeks time, respectively. Cellular behavior and inflammatory responses were assessed by means of histology staining and biochemical function and matrix deposition by immunohistochemistry. Additionally, both OC structures stability and new cartilage and bone formation were evaluated by using vivo- computed tomography (Scanco 80). The results showed no acute inflammatory response for both approaches. New tissue formation and integration in the adjacent tissues were also observed, which present different characteristic behaviors when comparing hydrogels and sponges response. As future insights, a novel strategy for regeneration of OC defects can be designed encompassing both, hydrogels and spongy-like structures and cellular approaches. References: 1. Espregueira-Mendes J. et al. Osteochondral transplantation using autografts from the upper tibio-fibular joint for the treatment of knee cartilage lesions. Knee Surgery, Sports Traumatology, Arthroscopy 20,1136, 2012. 2. Oliveira JM. et al, Novel hydroxyapatite/chitosan bilayered scaffold for osteochondral tissue-engineering applications: Scaffold design and its performance when seeded with goat bone marrow stromal cells. Biomaterials 27, 6123, 2006. 3. Pereira D R. et al. Gellan Gum-Based Hydrogel Bilayered Scaffolds for Osteochondral Tissue Engineering. Key Engineering Materials 587, 255, 2013.

Development of biomimetic microengineered hydrogel fibers for tendon regeneration

Musculoskeletal diseases are one of the leading causes of disability worldwide. Tendon injuries are responsible for substantial morbidity, pain and disability. Tissue engineering strategies aim at translating tendon structure into biomimetic materials. The main goal of the present study is to develop microengineered hydrogel fibers through the combination of microfabrication and chemical interactions between oppositely charged polyelectrolytes. For this, methacrylated hyaluronic acid (MeHA) and chondroitin sulfate (MeCS) were combined with chitosan (CHT). Hydrogel fibers were obtained by injecting polymer solutions (either MeHA or MeHA/MeCS and CHT) in separate microchannels that join at a y-junction, with the materials interacting upon contact at the interface. To evaluate cell behavior, human tendon derived cells (hTDCs) were isolated from tendon surplus samples during orthopedic surgeries and seeded on top of the fibers. hTDCs adhered to the surface of the fibers, remaining viable, and were found to be expressing CD44, the receptor for hyaluronic acid. The synthesis of hydrogel fibers crosslinkable through both physical and chemical mechanisms combined with microfabrication technology allows the development of biomimetic structures with parallel fibers being formed towards the replication of tendon tissue architecture.

Tendon regeneration through a scaffold-free approach: development of tenogenic magnetic hASCs sheets

Tendon's regeneration is limited, demanding for cell-based strategies to fully restore their functionality upon injury. The concept of magnetic force-based TE(1), generally using magnetic nanoparticles may enable, for example, stem cell stimulation and/or remote control over TE constructs. Thus, we originally propose the development of magnetic cell sheets (magCSs) with tenogenic capability, aimed at promoting tendon's regeneration. A Tenomodulin (TNMD+) subpopulation was sorted from human adipose stem cells (hASCs), using TNMD-coated immunomagnetic beads(2) and used as cell source for the development of magCSs. Briefly, cells were labeled with iron oxide composite particles (Micromod) and cultured for 7 days in α-MEM medium with or without magnetic stimulation provided by a magnetic device (nanoTherics). CSs were retrieved from the plates using magnet attraction as contiguous sheets of cells within its own deposited ECM.

Advancing tendon regeneration through the development of bio-stimulating tissue engineering approaches

Tendon tissue engineering (TE) requires tailoring scaffolds designs and properties to the anatomical and functional requirements of tendons located in different regions of the body. Cell sourcing is also of utmost importance as tendon cells are scarce. Recently, we have found that it is possible to direct the tenogenic differentiation of Amniotic fluid and Adipose tissue derived stem cells (hAFSCs and hASCs), and also that there are hASCs subpopulations that might be more prone to tenogenic differentiation. Nevertheless, biochemical stimulation may not be enough to develop functional TE substitutes for a tissue that is known to be highly dependent on mechanical loading.

Monitoring the early stiffness development in epoxy adhesives for structural strengthening

The present work aimed to assess the early-age evolution of E-modulus of epoxy adhesives used for Fibre-Reinforced Polymer (FRP) strengthening applications. The study involved adapting an existing technique devised for continuous monitoring of concrete stiffness since casting, called EMM-ARM (Elasticity Modulus Measurement through Ambient Response Method) for evaluation of epoxy stiffness. Furthermore, monotonic tensile tests according to ISO standards and cyclic tensile tests were carried out at several ages. A comparison between the obtained results was performed in order to better understand the performance of the several techniques in the assessment of stiffness of epoxy resins. When compared to the other methodologies, the method for calculation of E-modulus recommended by ISO standard led to lower values, since in the considered strain interval, the adhesive had a non-linear stress–strain relationship. The EMM-ARM technique revealed its capability in clearly identifying the hardening kinetics of epoxy adhesives, measuring the material stiffness growth during the entire curing period. At very early ages the values of Young׳s modulus obtained with quasi-static tests were lower than the values collected by EMM-ARM, due to the fact that epoxy resin exhibited a significant visco-elastic behaviour.

Development of benchmarks for operating costs and resources consumption to be used in healthcare building sustainability assessment methods

Since the last decade of the twentieth century, the healthcare industry is paying attention to the environmental impact of their buildings and therefore new regulations, policy goals and Buildings Sustainability Assessment (HBSA) methods are being developed and implemented. At the present, healthcare is one of the most regulated industries and it is also one of the largest consumers of energy per net floor area. To assess the sustainability of healthcare buildings it is necessary to establish a set of benchmarks related with their life-cycle performance. They are both essential to rate the sustainability of a project and to support designers and other stakeholders in the process of designing and operating a sustainable building, by allowing the comparison to be made between a project and the conventional and best market practices. This research is focused on the methodology to set the benchmarks for resources consumption, waste production, operation costs and potential environmental impacts related to the operational phase of healthcare buildings. It aims at contributing to the reduction of the subjectivity found in the definition of the benchmarks used in Building Sustainability Assessment (BSA) methods, and it is applied in the Portuguese context. These benchmarks will be used in the development of a Portuguese HBSA method.

Development of foam one-part geopolymers with enhanced thermal insulation performance and low carbon dioxide emissions

Buildings are responsible for more than 40% of the energy consumption and greenhouse gas emissions. Thus, increasing building energy efficiency is one the most cost-effective ways to reduce emissions. The use of thermal insulation materials could constitute the most effective way of reducing heat losses in buildings by minimising heat energy needs. These materials have a thermal conductivity factor, k (W/m.K) lower than 0.065 while other insulation materials such as aerated concrete can go up to 0.11. Current insulation materials are associated with negative impacts in terms of toxicity. Polystyrene, for example contains anti-oxidant additives and ignition retardants. In addition, its production involves the generation of benzene and chlorofluorocarbons. Polyurethane is obtained from isocyanates, which are widely known for their tragic association with the Bhopal disaster. Besides current insulation materials releases toxic fumes when subjected to fire. This paper presents experimental results on one-part geopolymers. It also includes global warming potential assessment and cost analysis. The results show that only the use of aluminium powder allows the production mixtures with a high compressive strength however its high cost means they are commercially useless when facing the competition of commercial cellular concrete. The results also show that one-part geopolymer mixtures based on 26%OPC +58.3%FA +8%CS +7.7%CH and 3.5% hydrogen peroxide constitute a promising cost efficient (67 euro/m3), thermal insulation solution for floor heating systems with low global warming potential of 443 KgCO2eq/m3.

Assessing the feasibility of impregnating phase change materials in lightweight aggregate for development of thermal energy storage systems

This paper assesses the feasibility of impregnation/encasement of phase change materials (PCMs) in lightweight aggregates (LWAs). An impregnation process was adopted to carry out the encasement study of two different PCMs in four different LWAs. The leakage of the impregnated/encased PCMs was studied when they were submitted to freeze/thawing and oven drying tests, separately. The results confirmed that, the impregnation/encasement method is effective with respect to the large thermal energy storage density, and can be suitable for applications were PCMs cannot be incorporated directly such as asphalt road pavements.

Development of sandwich panels of customized functionalities for the rehabilitation of the built patrimony

Considering that the future of the construction sector in most European countries will mainly lie in the renovation of the existing building stock, in the next coming years thousands of energy inefficient buildings will need renovation to force EU member states to reach the EU 2020 targets and implement the Energy Performance of Buildings Directive (EPBD). Seeing the actual crisis in the construction sector as an opportunity, this work aims to develop a concept for prefabricated customizable sandwich panels for the multifunctional renovation of buildings, focusing also on technological innovation. More than a conventional solution, this proposal aims to combine sustainable and recycled building materials, available technologies and systems with advanced design and manufacturing tools within an integrated and mass-customizable approach of advanced building renovation prefabricated solutions. The adoption of these new proposed solutions would improve the living standards of the inhabitants of our cities, reducing energy inefficiency and other existing construction/renovation problems, while enabling some advanced features like the incorporation of technical modules that could even monitor the building performance during its full lifetime and the living conditions of its occupants.

Development of innovative hybrid sandwich panel slabs: Experimental results

The authors appreciate the collaboration of the following labs: Civitest for developing DHCC materials, PIEP for conducting VARTM process (Eng. Luis Oliveira) and Department of Civil Engineering of Minho University to perform the tests (Mr. Antonio Matos and Eng. Marco Jorge).

The impact of PBL on transferable skills development in management education

Attention to transferable skills is growing in higher education. Problem-based learning (PBL) is increasingly used in management education for its promising potential to, amongst others, promote transferable skills, including problem-solving, critical thinking and teamwork skills. However, this relationship is seldom assessed. In this study, I use structural equation modelling to examine the effectiveness of PBL, measured through students’ perceptions of satisfaction and skills development. Results show the development of transferable skills is explained by interaction with tutors and a host company, and defining teamwork rules. Satisfaction is explained by skills development, assessment issues, defining teamwork rules and understanding how organisations work. I draw conclusions and recommendations.

Thermo-compression molding of chitosan with a deep eutectic mixture for biofilms development

Supplementary information available at: http://www.rsc.org/suppdata/c5/gc/c5gc02231b/c5gc02231b1.pdf

Development of autonomous maintenance in a furniture company

This article presents a work performed in the maintenance department of a furniture company in Portugal, in order to develop and implement autonomous maintenance. The main objective of the project was related to the objective to increase and make effective the autonomous maintenance tasks performed by production operators, and in this way avoiding unplanned downtime due to equipment failures. Although some autonomous maintenance tasks were already carried out within the company, a preliminary study revealed weaknesses in the application of this tool. In the initial phase of this pilot project, the main problems encountered at the level of autonomous maintenance were related to the lack of time to carry out these tasks, showing that the stipulated procedures were far from the real needs of the company. To solve these problems a pilot project was conducted, making several changes in the performance of autonomous maintenance tasks, making them standard and adapted to reality of each production line. There was a general improvement in the factory indicators, and essentially there was a behavioral change, since the operators felt that their opinions were taking into account and began to understand the importance of small tasks performed by them.

HEP-Frame: A software engineered framework to aid the development and efficient multicore execution of scientific code

This work was supported by FCT (Fundação para a Ciência e Tecnologia) within Project Scope (UID/CEC/00319/2013), by LIP (Laboratório de Instrumentação e Física Experimental de Partículas) and by Project Search-ON2 (NORTE-07-0162- FEDER-000086), co-funded by the North Portugal Regional Operational Programme (ON.2 - O Novo Norte), under the National Strategic Reference Framework, through the European Regional Development Fund.